ABSTRACT
Objective To observe toxic symptoms and signs , toxic damage extents and reversibility in rats after oral administration of Tangwang Mingmu granules .Methods Four dose groups with 40 rats in each group were designed in this study, including control group fed with distilled water and three groups at different dosages of the test drug .Tangwang Mingmu granules were orally administered to SD rats at the dosage of 8.4, 4.2 and 2.1 g/kg for 3 weeks and 14.0, 8.4 and 4.2 g/kg for 23 weeks, for 26 consecutive weeks .The general state of the rats was observed every day , while body mass and food consumption were calculated once a week .Halfway through and at the end of the administration (13 and 26 weeks) and after four weeks of recovery, parameters of body mass, hematology, hematological biochemistry, organ/body mass ratio and histopathology were measured .Results Compared with the control group at the same time-point, body mass of male rats in the other three groups was slightly reduced .Food consumption in high and medium dose groups was reduced (P<0.05), MCHC, ALT, TBIL and Na +in high dose group were decreased (P<0.05), TP, ALB and D-BIL were increased (P<0.05), the mean body mass and relative organ weight of thymus in medium dose male rats were decreased (P<0.05), relative organ weight of the liver and kidney in high dose male rats was increased (P<0.05), and focal chronic inflammation to different extent was observed in the liver , kidney and prostate gland .No dose-effect relationship was found in these perturbations that were all within the normal range of animals .No significant drug-related pathological changes were found.Conclusion The NOAEL of Tangwang Mingmu granules is considered to be 14.0 g/kg body mass/day (equal to 50 times the proposed clinical adult dosage ) for the 26-week repeated dose oral toxicity study in male andfemale rats.
ABSTRACT
The purpose of risk assessment is to evaluate the permissible exposure level under specific risk factors.To extrapolate the human acceptable daily intake (ADI) and/or reference dose (RfD), the traditional method uses the no-observed-adverse-effect level ( NOAEL ) to quantify toxicity after being divided by uncertainty factor.There are many limitations with NOAEL method in safety evaluation,for it relies too much on experimental design.Benchmark dose ( BMD) approach is a more reliable method with many advantages.BMD approach and its analysis software, the advantages of BMD over NOAEL, the application and methodological perfection in risk assessment of long-team exposure toxicity are presented in this review.
ABSTRACT
Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners( PCBs) and high fat diet alone or in combination.Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet.Urine samples were collected after 6-week treatment, 1 H NMR spectra were performed and analyzed by principal component analysis ( PCA) . Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism.The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide ( TMAO) in the combined exposure group after six-week exposure.Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle (TAC).These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids.The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.